Fig. 4.   Two different approaches to animal models of nicotine administration. The injection route produces peak plasma levels that exceed the threshold for fetal hypoxia-ischemia, with episodic recovery in between doses. Similar events occur in cigarette smoking, which superimposes the effects of nicotine on episodic hypoxia-ischemia. The infusion route, via minipump implants, produces a steady-state plasma level that can be adjusted to fall below the threshold for fetal hypoxia-ischemia and that can maintain levels found in smokers. Infusions closely resemble human exposures via transdermal nicotine patches.